Inhibition of tumor growth and induction of apoptosis in prostate cancer cell lines by overexpression of tissue inhibitor of matrix metalloproteinase-3

Zhang, L; Zhao, Lijing; Zhao, Dongxu; Lin, Guimiao; Guo, Baofeng; Li, Y; Zhu, Liang; Zhao, Xin; Fang, Xuedong

doi:10.1038/cgt.2009.59

Cited by 31 publications

(32 citation statements)

References 44 publications

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“…Because prostate cancer represents an accumulation of genetic mutations in cells that have gone awry, a novel approach against this cancer is gene therapy. 20 Signal transducers and activators of transcription (STAT) proteins are a family of seven proteins (Stats 1, 2, 3, 4, 5a, 5b and 6) that mediate the transduction of extracellular signals to the transcription of target genes. Among the STATs, Stat3 is the most important, being closely linked to tumourigenesis.…”

Section: Discussionmentioning

confidence: 99%

Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo

Zhu¹,

Guo²,

Li³

et al. 2011

Asian J Androl

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DNA vector-based Stat3-specific RNA interference (si-Stat3) blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BL/6 mice. CaCl 2 -modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Stat3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGF and cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% (P,0.01). Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis (up to 42%, P,0.01). The Stat3 downstream genes Bcl-2, VEGF and cyclin D1 were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.

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Section: Discussionmentioning

confidence: 99%

Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo

Zhu¹,

Guo²,

Li³

et al. 2011

Asian J Androl

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“…16 Proteins of interest were detected using Survivin and b-actin antibodies from Santa Cruz Biotech according to the manufacture's protocol. GRIM-19 antibody was applied as before.…”

Section: Western Blottingmentioning

confidence: 99%

“…It is a growth suppressive gene product in the IFN and retinoic acid-induced cell death pathway. 16 Accumulating data has revealed that a GRIM-19 mutation plays a role in the development/progression of thyroid carcinoma plus the low expression of GRIM-19 has been observed in some primary human renal and PCas. 17,18 Accumulating data indicated that most tumors express high levels of signal transducer and activator of transcription 3 (Stat3), which is known to upregulate the expression of Survivin.…”

Section: Introductionmentioning

confidence: 99%

Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

Liu

Zhang²,

Guo³

et al. 2012

Asian J Androl

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Persistent activation of Survivin and its overexpression contribute to the formation, progression and metastasis of several different tumor types. Therefore, Survivin is an ideal target for RNA interference mediated-growth inhibition. Blockade of Survivin using specific short hairpin RNAs (shRNA) can significantly reduce prostate tumor growth. RNA interference does not fully ablate target gene expression, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Survivin-specific shRNA, we employed a combinatorial expression of Survivin-specific shRNA and gene associated with retinoid-interferon-induced mortality-19 (GRIM-19). Then, the GRIM-19 coding sequences and Survivin-specific shRNAs were used to create a dual expression plasmid vector and were carried by an attenuated strain of Salmonella enteric serovar typhimurium (S. typhimurium) to treat prostate cancer in vitro and in vivo. We found that the co-expressed Survivin-specific shRNA and GRIM-19 synergistically and more effectively inhibited prostate tumor proliferation and survival, when compared with treatment with either single agent alone in vitro and in vivo. This study has provided a novel cancer gene therapeutic approach for prostate cancer.

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“…[14][15][16][17] TIMP-3 can inhibit invasion and induce cell apoptosis in some specific cancer cell strains. [18][19][20][21][22] These observations indicate that TIMP-3 expressed within the tumor microenvironment exerts suppressive effects on tumorigenesis and metastatic colonization, mainly because of its antiangiogenic activity. Indeed, the immune system and the inflammatory factors have been reported crucial in regulation of angiogenesis.…”

Section: Introductionmentioning

confidence: 96%

Regulation of Th1/Th2 polarization by tissue inhibitor of metalloproteinase-3 via modulating dendritic cells

Shao

Ning

et al. 2012

Blood

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Tissue inhibitor of metalloproteinase-3 (TIMP-3) is one of a family of proteins inhibiting matrix metalloproteinases, which has also been identified as a mediator for checking inflammation. Meanwhile, it is well known that inflammation causes the activation of the immune response. However, it is not clear whether TIMP-3 plays a role in the immune system. In the present study, we demonstrated a novel function of TIMP-3 in Th1/Th2 polarization through its influence on the antigen-presenting cells. First, TIMP-3 was found strikingly up-regulated by IL-4 during the differentiation of human dendritic cells via the p38MAPK pathway. Second, the expression of costimulatory molecule-CD86 was repressed by TIMP-3. Besides, the induction of IL-12 in matured dendritic cells was significantly inhibited in a PI3K-dependent manner. IntroductionDendritic cells (DCs) are thought to be indispensable to initiate primary immune responses and play a pivotal role in linking the innate immunity and the adaptive immunity. 1,2 Their functions directly determine the outcome of T helper (Th) cell-mediated immune responses. 3,4 Normally, DCs reside in almost every tissue where they keep an immature state (imDCs) and serve as sentinels for the "dangerous" antigens. On stimulation with antigens or other signals, they undergo maturation and the matured DCs (mDCs) then migrate to the draining lymph nodes, where they present antigens to naive T cells. 5,6 In addition to their antigen presenting capability executed by the MHC class II molecules and the costimulatory molecules (CD40, CD80, and CD86), DCs also manipulate the nature and extent of the T cell-mediated immune responses through producing a variety of cytokines in response to the TLR ligands. 7 IL-12, which is deemed as a critical signal in T-cell polarization, together with IFN-␥, instructs naive T cell to shift toward a Th1 response, whereas IL-4 and a low level of IL-12 cause a Th2 response. In addition, the generation of regulatory T (Treg) cells requires 5,8,9 Therefore, the tissue environmental factors profoundly influence the adaptive immune responses through their modulation on DCs.Tissue inhibitors of metalloproteinases (TIMPs), specific inhibitors of matrix metalloproteinases (MMPs), consist of a family of 4 proteins that have been characterized so far. Independent of their inhibitory ability on MMPs, they also perform other biologic activities, such as promotion of cell proliferation, proapoptotic and antiapoptotic, and synaptic plasticity activities. 10,11 TIMP-3, a unique member of this family, is mainly sequestered to tissue extracellular matrix and is the only TIMP capable of inhibiting membrane bound MMPs, transmembrane MMPs, and sheddases, such as TNF-␣ converting enzyme. 12,13 TIMP-3 has been shown to act as a tumor suppressor in different cancer types, and loss of TIMP3 is closely associated with acquisition of tumorigenesis. 14-17 TIMP-3 can inhibit invasion and induce cell apoptosis in some specific cancer cell strains. [18][19][20][21][22] These observations indica...

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Inhibition of tumor growth and induction of apoptosis in prostate cancer cell lines by overexpression of tissue inhibitor of matrix metalloproteinase-3

Cited by 31 publications

References 44 publications

Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo

Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo

Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

Regulation of Th1/Th2 polarization by tissue inhibitor of metalloproteinase-3 via modulating dendritic cells

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